Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells
This study determines the effect of naked and heparinbased
super-paramagnetic iron oxide nanoparticles on the human
cancer cell lines of A2780. Doxorubicin was used as the anticancer
drug, entrapped in the SPIO-NPs. This study aimed to decorate
nanoparticles with heparin, a molecular ligand for 'active' targeting
of cancerous cells and the application of modified-nanoparticles in
cancer treatment. The nanoparticles containing the anticancer drug
DOX were prepared by a solvent evaporation and emulsification
cross-linking method. The physicochemical properties of the
nanoparticles were characterized by various techniques, and uniform
nanoparticles with an average particle size of 110±15 nm with high
encapsulation efficiencies (EE) were obtained. Additionally, a
sustained release of DOX from the SPIO-NPs was successful.
Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell
toxicity than the individual HP and confocal microscopy analysis
confirmed excellent cellular uptake efficiency. These results indicate
that HP based SPIO-NPs have potential uses as anticancer drug
carriers and also have an enhanced anticancer effect.
[1] S. Nie, Y. Xing, G. J. Kim, and J. W. Simons, "Nanotechnology
applications in cancer," Annu. Rev. Biomed. Eng. Vol. 9, pp. 257-288,
2007.
[2] C. C. M. You, O. R. Gider, B. Ghosh, S. P. Kim, I. Erdogan, B. Krovi,
S. A. Bunz, U. H. F. Rotello, "Detection and identification of proteins
using nanoparticle? Fluorescent polymer ÔÇÿchemical nose- sensors,"
Nature Nanotech. Vol. 2, pp. 318-323, 2007.
[3] M. Ferrari, "Cancer nanotechnology: opportunities and challenges," Nat
Rev Cancer, vol. 5, pp. 161-71, 2005.
[4] S. Kommareddy, and M. Amiji, "Preparation and evaluation of thiolmodified
gelatin nanoparticles for intracellular DNA delivery in
response to glutathione," Bioconjug. Chem. vol. 16, 1423-1432, 2005.
[5] D. B. Pike, S. Cai, K. R. Pomraning, M. A. Firpo, R. J. Fisher, and X. Z.
Shu, "Heparinregulated release of growth factors in vitro and angiogenic
response in vivo to implanted hyaluronan hydrogels containing VEGF
and bFGF," Biomaterials, vol. 27, pp. 5242-5251, 2006.
[6] R. J. Linhardt, "Heparin-induced cancer cell death," Chem. Biol. vol. 11,
pp. 420-422, 2007.
[7] M. K. Yu, D. Y. Lee, Y. S. Kim, K. Park, S. A. Park, and D. H. Son,
"Antiangiogenic and apoptotic properties of a novel amphiphilic folate-
heparin-lithocholate derivative having cellular internality for cancer
therapy," Pharm. Res. vol. 24, pp. 705-14, 2007.
[8] Q. L. Guo, Q. D. You, Z. Q. Wu, S. T. Yuan, and L. Zhao, "General
gambogic acids inhibited growth of human hepatoma SMMC-7721 cells
in vitro and in nude mice," Acta Pharmacol. Sin. vol. 25, pp. 769-774,
2004.
[9] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase
reverse transcriptase gene expression by gambogic acid in human
hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[10] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase
reverse transcriptase gene expression by gambogic acid in human
hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[11] T. T. Wang, J. Wei, X. P. Qian, Y. T. Ding, L. X. Yu, and B. R. Liu,
"Gambogic acid, a potent inhibitor of survivin, reverses docetaxel
resistance in gastric cancer cells," Cancer Lett. vol. 262, pp. 214-222,
2008.
[12] K. K. Gilles, and I. Joseph, "A nanoparticle-based immobilization assay
for prion-kinetics study," J. Nanobiotechnol. Vol. 4, pp. 8-16, 2006.
[13] B. L. Lin, X. D. Shen, and S. Cui, "Application of nanosized Fe3O4 in
anticancer drug carriers with target-orientation and sustained-release
properties," Biomed. Mater. vol. 2, pp. 132-134, 2007.
[14] J. C. Reed, "Regulation of apoptosis by bcl-2 family proteins and its role
in cancer and chemoresistance," Curr. Opin. Oncol. Vol. 7, pp. 541-
546, 1995.
[15] B. A. Chen, Q. Sun, and X. M. Wang, "Reveral in multidrug resistance
by magnetic nanoparticle of Fe3O4 loaded with adriamycin and
tetrandrine in K562/AO2 leukemic cells," Int. J. Nanomedicine, vol. 3,
pp. 277-286, 2008.
[16] B. A. Chen, J. Cheng, and Y. N. Wu, "Reversal of multidrug resistance
by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-
bromotetrandrine in xenograft nude-mice," Int. J. Nanomedicine, vol. 4,
pp. 73-78, 2009.
[17] B. A. Chen, J. Cheng, and M. F. Shen, "Magnetic nanoparticle of Fe3O4
and 5-bromotetrandrin interact synergistically to induce apoptosis by
daunorubicin in leukemia cells," Int. J. Nanomedicine, vol. 4, pp. 65-71,
2009.
[18] K. Yacobi, A. Wojtowicz, A. Tsafriri, and A. Gross, "Gonadotropins
enhance caspase-3 and -7 activity and apoptosis in the theca-interstitial
cells of rat preovulatory follicles in culture," Endocrinol. Vol. 145, pp.
1943-1951, 2004.
[19] N. Takai, T. Ueda, M. Nishida, K. Nasu, and K. Miyakawa, "The
relationship between oncogene expression and clinical outcome in
endometrial carcinoma," Curr. Cancer Drug Targets, vol. 4, pp. 511-
520, 2004.
[20] D. C. Altieri, "Survivin, versatile modulation of cell division and
apoptosis in cancer," Oncogene. vol. 22, pp. 8581-8589, 2003.
[21] X. Ling, R. J. Bernacki, M. G. Brattain, and F. Z. Li, "Induction of
survivin expression by taxol (paclitaxel) is an early event,which is
independent of taxol mediated G2/M arrest," J. Biol. Chem. vol. 279,
pp. 15196-15203, 2004.
[22] S. P. Tu, J. T. Cui, and P. Liston, "Gene therapy for colon cancer by
adenoassociated viral vector-mediated transfer of survivin Cys84Ala
mutant," Gastroenterol. vol. 128, pp. 361-375, 2005.
[23] D. C. Altieri, "Validating survivin as a cancer therapeutic target," Nat.
Rev. Cancer, vol. 3, pp. 46-54, 2003.
[24] J. M. Adams, and S. Cory, "The Bcl-2 protein family: arbiters of cell
survival," Science.vol. 281, pp. 1322-1326, 1998.
[25] H. J. M. M. Mertens, M. J. Heineman, and J. L. H. Evers, "The
expression of apoptosis-related proteins bcl-2 and ki67 in endometrium
of ovulatory men strual cycles," Gynecol. Obstet. Invest. vol. 53, pp.
224-230, 2002.
[26] C. M. J. L. Tilli, A. J. W. Stavast-Koey, F. C. S. Ramaekers, and H. A.
M. Neumann, "Bax expression and growth behavior of basal cell
carcinomas," J. Cutan. Pathol. vol. 29, pp. 79-87, 2002.
[27] F. Pettersson, A. G. Dalgleish, R. P. Bissonnette, and K. W. Colston,
"Retinoids cause apoptosis in pancreatic cancer cells via activation of
RAR-gamma and altered expression of Bcl-2/Bax," Br. J. Cancer. vol.
87, pp. 555-561, 2002.
[28] V. Kirkin, S. Joos, and M. Zornig, "The role of Bcl-2 family members in
tumorigenesis," Biochim. Biophys. Acta. vol. 1644, pp. 229-249, 2004.
[29] A. Suzuki, T. Ito, and M. Hayashida, "Survivin initiates procaspase
3/p21 complex formation as a result of interaction with Cdk4 to resist
Fas-mediated cell death," Oncogene. vol. 19, pp. 1346-1353, 2000.
[1] S. Nie, Y. Xing, G. J. Kim, and J. W. Simons, "Nanotechnology
applications in cancer," Annu. Rev. Biomed. Eng. Vol. 9, pp. 257-288,
2007.
[2] C. C. M. You, O. R. Gider, B. Ghosh, S. P. Kim, I. Erdogan, B. Krovi,
S. A. Bunz, U. H. F. Rotello, "Detection and identification of proteins
using nanoparticle? Fluorescent polymer ÔÇÿchemical nose- sensors,"
Nature Nanotech. Vol. 2, pp. 318-323, 2007.
[3] M. Ferrari, "Cancer nanotechnology: opportunities and challenges," Nat
Rev Cancer, vol. 5, pp. 161-71, 2005.
[4] S. Kommareddy, and M. Amiji, "Preparation and evaluation of thiolmodified
gelatin nanoparticles for intracellular DNA delivery in
response to glutathione," Bioconjug. Chem. vol. 16, 1423-1432, 2005.
[5] D. B. Pike, S. Cai, K. R. Pomraning, M. A. Firpo, R. J. Fisher, and X. Z.
Shu, "Heparinregulated release of growth factors in vitro and angiogenic
response in vivo to implanted hyaluronan hydrogels containing VEGF
and bFGF," Biomaterials, vol. 27, pp. 5242-5251, 2006.
[6] R. J. Linhardt, "Heparin-induced cancer cell death," Chem. Biol. vol. 11,
pp. 420-422, 2007.
[7] M. K. Yu, D. Y. Lee, Y. S. Kim, K. Park, S. A. Park, and D. H. Son,
"Antiangiogenic and apoptotic properties of a novel amphiphilic folate-
heparin-lithocholate derivative having cellular internality for cancer
therapy," Pharm. Res. vol. 24, pp. 705-14, 2007.
[8] Q. L. Guo, Q. D. You, Z. Q. Wu, S. T. Yuan, and L. Zhao, "General
gambogic acids inhibited growth of human hepatoma SMMC-7721 cells
in vitro and in nude mice," Acta Pharmacol. Sin. vol. 25, pp. 769-774,
2004.
[9] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase
reverse transcriptase gene expression by gambogic acid in human
hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[10] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase
reverse transcriptase gene expression by gambogic acid in human
hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[11] T. T. Wang, J. Wei, X. P. Qian, Y. T. Ding, L. X. Yu, and B. R. Liu,
"Gambogic acid, a potent inhibitor of survivin, reverses docetaxel
resistance in gastric cancer cells," Cancer Lett. vol. 262, pp. 214-222,
2008.
[12] K. K. Gilles, and I. Joseph, "A nanoparticle-based immobilization assay
for prion-kinetics study," J. Nanobiotechnol. Vol. 4, pp. 8-16, 2006.
[13] B. L. Lin, X. D. Shen, and S. Cui, "Application of nanosized Fe3O4 in
anticancer drug carriers with target-orientation and sustained-release
properties," Biomed. Mater. vol. 2, pp. 132-134, 2007.
[14] J. C. Reed, "Regulation of apoptosis by bcl-2 family proteins and its role
in cancer and chemoresistance," Curr. Opin. Oncol. Vol. 7, pp. 541-
546, 1995.
[15] B. A. Chen, Q. Sun, and X. M. Wang, "Reveral in multidrug resistance
by magnetic nanoparticle of Fe3O4 loaded with adriamycin and
tetrandrine in K562/AO2 leukemic cells," Int. J. Nanomedicine, vol. 3,
pp. 277-286, 2008.
[16] B. A. Chen, J. Cheng, and Y. N. Wu, "Reversal of multidrug resistance
by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-
bromotetrandrine in xenograft nude-mice," Int. J. Nanomedicine, vol. 4,
pp. 73-78, 2009.
[17] B. A. Chen, J. Cheng, and M. F. Shen, "Magnetic nanoparticle of Fe3O4
and 5-bromotetrandrin interact synergistically to induce apoptosis by
daunorubicin in leukemia cells," Int. J. Nanomedicine, vol. 4, pp. 65-71,
2009.
[18] K. Yacobi, A. Wojtowicz, A. Tsafriri, and A. Gross, "Gonadotropins
enhance caspase-3 and -7 activity and apoptosis in the theca-interstitial
cells of rat preovulatory follicles in culture," Endocrinol. Vol. 145, pp.
1943-1951, 2004.
[19] N. Takai, T. Ueda, M. Nishida, K. Nasu, and K. Miyakawa, "The
relationship between oncogene expression and clinical outcome in
endometrial carcinoma," Curr. Cancer Drug Targets, vol. 4, pp. 511-
520, 2004.
[20] D. C. Altieri, "Survivin, versatile modulation of cell division and
apoptosis in cancer," Oncogene. vol. 22, pp. 8581-8589, 2003.
[21] X. Ling, R. J. Bernacki, M. G. Brattain, and F. Z. Li, "Induction of
survivin expression by taxol (paclitaxel) is an early event,which is
independent of taxol mediated G2/M arrest," J. Biol. Chem. vol. 279,
pp. 15196-15203, 2004.
[22] S. P. Tu, J. T. Cui, and P. Liston, "Gene therapy for colon cancer by
adenoassociated viral vector-mediated transfer of survivin Cys84Ala
mutant," Gastroenterol. vol. 128, pp. 361-375, 2005.
[23] D. C. Altieri, "Validating survivin as a cancer therapeutic target," Nat.
Rev. Cancer, vol. 3, pp. 46-54, 2003.
[24] J. M. Adams, and S. Cory, "The Bcl-2 protein family: arbiters of cell
survival," Science.vol. 281, pp. 1322-1326, 1998.
[25] H. J. M. M. Mertens, M. J. Heineman, and J. L. H. Evers, "The
expression of apoptosis-related proteins bcl-2 and ki67 in endometrium
of ovulatory men strual cycles," Gynecol. Obstet. Invest. vol. 53, pp.
224-230, 2002.
[26] C. M. J. L. Tilli, A. J. W. Stavast-Koey, F. C. S. Ramaekers, and H. A.
M. Neumann, "Bax expression and growth behavior of basal cell
carcinomas," J. Cutan. Pathol. vol. 29, pp. 79-87, 2002.
[27] F. Pettersson, A. G. Dalgleish, R. P. Bissonnette, and K. W. Colston,
"Retinoids cause apoptosis in pancreatic cancer cells via activation of
RAR-gamma and altered expression of Bcl-2/Bax," Br. J. Cancer. vol.
87, pp. 555-561, 2002.
[28] V. Kirkin, S. Joos, and M. Zornig, "The role of Bcl-2 family members in
tumorigenesis," Biochim. Biophys. Acta. vol. 1644, pp. 229-249, 2004.
[29] A. Suzuki, T. Ito, and M. Hayashida, "Survivin initiates procaspase
3/p21 complex formation as a result of interaction with Cdk4 to resist
Fas-mediated cell death," Oncogene. vol. 19, pp. 1346-1353, 2000.
@article{"International Journal of Medical, Medicine and Health Sciences:49696", author = "Amaneh Javid and Shahin Ahmadian and Ali A. Saboury and Saeed Rezaei-Zarchi", title = "Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells", abstract = "This study determines the effect of naked and heparinbased
super-paramagnetic iron oxide nanoparticles on the human
cancer cell lines of A2780. Doxorubicin was used as the anticancer
drug, entrapped in the SPIO-NPs. This study aimed to decorate
nanoparticles with heparin, a molecular ligand for 'active' targeting
of cancerous cells and the application of modified-nanoparticles in
cancer treatment. The nanoparticles containing the anticancer drug
DOX were prepared by a solvent evaporation and emulsification
cross-linking method. The physicochemical properties of the
nanoparticles were characterized by various techniques, and uniform
nanoparticles with an average particle size of 110±15 nm with high
encapsulation efficiencies (EE) were obtained. Additionally, a
sustained release of DOX from the SPIO-NPs was successful.
Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell
toxicity than the individual HP and confocal microscopy analysis
confirmed excellent cellular uptake efficiency. These results indicate
that HP based SPIO-NPs have potential uses as anticancer drug
carriers and also have an enhanced anticancer effect.", keywords = "Heparin, A2780 cells, ovarian cancer, nanoparticles,doxorubicin.", volume = "5", number = "2", pages = "32-5", }
